Impact of PAC, a curcumin analog on the radiosensitivity of breast cancer cells

Identifying agents that block the signaling pathway of nuclear factor kappa-light-13 chain-enhancer of activated B cells (NF-κB) is a key strategy in addressing inflammation, cancer progression, and treatment resistance. Natural compounds such as curcumin have demonstrated notable biological activity, but their clinical application is restricted by poor pharmacokinetics, including low bioavailability and rapid metabolism. To overcome these limitations, 3, 5-bis (4-hydroxy-3-methoxybenzylidene)-1-methylpiperidin-4-one (PAC), a synthetic curcumin analog developed in our laboratory, was investigated in MCF-7 and MDA-MB-231 human breast cancer cell lines. Focusing on estimated PAC’s effects on apoptosis, cell viability, colony formation, and the expression of tumor protein 53 (p53), NF-κB, Bcl-2-associated X protein (Bax), and B-cell lymphoma 2 (Bcl-2). at both gene and protein levels. PAC triggered apoptosis and slowed cell growth in both cell lines, with stronger effects at higher doses. It also made these cells much more sensitive to radiation. The Chou-Talalay method confirmed a synergistic effect (Combination Index < 1) between PAC and radiation, especially at higher radiation doses. Mechanistically, the anticancer properties of PAC were reflected in its ability to inhibit NF-κB signaling and shift the balance of apoptosis-related factors, including p53, Bax, and Bcl-2, which contribute to treatment resistance. These findings suggest PAC may serve as a novel adjuvant therapy for breast cancer by enhancing radiosensitivity and improving patient outcomes. Additional clinical and preclinical studies are required to confirm its therapeutic potential.